DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for clear cell renal carcinoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleClear cell renal carcinoma maps to a 47-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedSunitinibApproved drugapprovedPazopanibApproved drug
Structures already discussed alongside clear cell renal carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
For clear cell renal carcinoma, the treatment landscape has shifted to combination therapies in the first-line setting. A 2021 review notes that both doublet immune checkpoint blockade and vascular endothelial growth factor receptor plus PD-1 blockade have achieved durable disease control and prolonged overall survival in randomised phase 3 trials. The same review cautions that differences in baseline patient characteristics, statistical plans, follow-up length, biomarker approaches, and trial design make cross-trial comparisons difficult. A 2022 case-based discussion reiterates that multiple options for systemic targeted and immune therapies exist, but does not report new survival or response data from a controlled trial.
Earlier work from 2011 describes six agents approved for advanced renal cell carcinoma, with treatment choice guided by disease setting, histology, patient characteristics, and comorbidities. A 2016 trial specifically addresses non-clear-cell renal cancer, noting that drug development has focused on clear-cell disease and that optimal therapy for non-clear-cell histologies remains unclear. A 2009 review states that anti-angiogenic agents provide robust response rates and progression-free survival advantages over historic therapy in clear-cell disease, but does not give concrete numbers for any single agent.
What is still missing is prospective biomarker-driven stratification to match patients to specific combinations, randomised data comparing the approved doublet regimens head-to-head, and dedicated trials for non-clear-cell histologies that report survival endpoints. The 2021 review explicitly calls for thoughtful study design to accurately estimate outcomes and integrate novel approaches.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA Oncology · 2016 · 80 citations
Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer
AbstractIMPORTANCE: The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain. OBJECTIVE: To establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer. DESIGN, SETTING, AND PARTICIPANTS: Single-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months. INTERVENTIONS: Patients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression. MAIN OUTCOMES AND MEASURES: The primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis. RESULTS: Of 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n = 13) and patient choice (n = 9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P = .05) and significant reduction in expression of von Hippel-Lindau tumor suppressor (100 vs 40; P < .001) and C-MET (300 vs 100; P < .001) and increased programmed cell death ligand 1 expression (0 vs 1.5; P < .001) in the immune component. No on-treatment biomarker correlated with response. CONCLUSIONS AND RELEVANCE: Nephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer.
Treatment Selection in First-line Metastatic Renal Cell Carcinoma—The Contemporary Treatment Paradigm in the Age of Combination Therapy
AbstractIMPORTANCE: The treatment landscape of metastatic renal cell carcinoma has evolved rapidly over the last decade. Recent combination approaches heralded by targeting immune checkpoints cytotoxic T-lymphocyte antigen 4 and programmed death-1 (PD-1) have been followed in consecutive years by protocols targeting vascular endothelial growth factor receptor, PD-1, and programmed death ligand-1. The differences in baseline patient characteristics, statistical plans, follow-up length, biomarker-derived approaches, and trial design make cross-trial comparisons difficult. Given the regulatory approval of a number of these regimens, the current available evidence is reviewed herein for combination first-line regimens with published randomized phase 3 trial data. OBSERVATIONS: Combination approaches have transformed outcomes for patients. Durable disease control and prolonged overall survival have been achieved by both doublet immune checkpoint blockade and vascular endothelial growth factor receptor plus PD-1 blockade. Rationale for variations in trial outcome are offered, alongside approaches to navigating patient-empowered treatment selection, focusing on predictive tools, biomarkers, and the role of real-world data. CONCLUSIONS AND RELEVANCE: Advances in the genomic, molecular, and immunologic understanding of metastatic clear cell renal cell carcinoma have lifted the survival curves for this disease markedly in recent years. Combination approaches will remain standard of care in the first-line setting. However, thoughtful study design is needed to accurately estimate outcomes and integrate novel approaches into the treatment armamentarium.
Therapeutic Advances in Medical Oncology · 2020 · 21 citations · open access
Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review
AbstractBACKGROUND: Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC. METHODS: We conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible. RESULTS: = 12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5 months and median overall survival of 17.3-31.0 months. Grade 3-4 adverse events rates were 21-55%. CONCLUSION: The present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.
Treatment Options for De Novo Metastatic Clear-cell Renal Cell Carcinoma: Current Recommendations and Future Insights.
AbstractThis clinical case-based discussion focuses on a 73-yr-old man diagnosed with intermediate-risk oligometastatic clear-cell renal cell carcinoma (RCC) and treated with systemic therapy. Current guideline-based treatment options are presented and critically examined. The discussion covers the main aspects of the management of metastatic RCC, such as the role of cytoreductive nephrectomy and metastasis-directed therapies, as well as the multiple options for systemic targeted and immune therapies. An insight into developments that may play a role in treatment pathways in the future according to the latest scientific advances is also provided. PATIENT SUMMARY: A number of treatment options are available for patients who have metastatic disease when diagnosed with clear-cell kidney cancer. Starting from a clinical case, the current standard of care and future perspectives regarding treatment of this disease are presented.
Journal of the National Comprehensive Cancer Network · 2011 · 9 citations · open access
Selecting Targeted Therapies for Patients With Renal Cell Carcinoma
AbstractAdvanced renal cell carcinoma (RCC) is a heterogeneous disease with variable histology, biology, and response to treatment. In the past 5 years, 6 new agents have been approved for the treatment of RCC, and many more are in clinical development. With an ever-increasing number of treatment options, selecting among them for a particular patient can be a daunting task for clinicians. This article describes how treatment choice can be guided by the disease setting and histology, as well as patient characteristics, comorbidities, and preference within the context of available data. Results from clinical trials are combined with practical considerations to make recommendations for first-line and subsequent treatment of patients with clear cell and non-clear cell RCC. These recommendations should supplement the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of advanced RCC.
Sunitinib vs. Everolimus for Advanced Non–Clear-Cell Renal Cancer
AbstractDrug development for advanced renal cell carcinoma during the past decade has focused on clear-cell disease, which represents 75% to 80% of all renal cell cancers. A few patients with non–clear-cell histologies have been included in advanced renal cancer phase III trials, but the optimal therapy for these patients remains unclear.
Now, international investigators have conducted an industry-sponsored, randomized, …
Additional Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
AbstractThe biology of clear-cell renal cell carcinoma (RCC) supports that anti-angiogenic agents may have therapeutic effect. Indeed, several agents have been shown to provide robust response rates and progression-free survival advantages over historic therapy. In addition, several newer agents are being tested in metastatic RCC. These agents including pazopanib, AZD2171 and PTK787 have demonstrated preclinical activity and have entered clinical trials. These novel agents are likely to add to the therapeutic armamentarium in RCC.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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